ALPHA-ADRENERGIC RECEPTOR BINDING

现在很清楚的是，有一个不同的受体大家族 去甲肾上腺素(NE)和肾上腺素(EPI)。至少7种药理作用 不同的肾上腺素能受体亚型(βL-，β2-，β3-，α1a-， Alpha1b-、Alpha2a-、Alpha2b-)已经被鉴定。 然而，关于这些亚型的重要性的信息很少 作为对发射机的响应。因为它们通常共存于细胞上，并具有 在相同的第二信使系统上的主要动作，净响应 发射器通常由多个 子类型。 我们的主要假设是去甲肾上腺素和肾上腺素通过 同时激活许多不同的受体亚型，这些 子类型以复杂的方式交互以确定 手机。我们建议使用一天龄大鼠脑的原代培养 表征第二信使对个别亚型的反应，澄清 它们的相互作用，并决定了细胞对递质的反应 是受控制的。 将实现以下具体目标： 1.确定第二信使参与的受体亚型 对NE和EPI的反应。烷基化试剂和竞争性拮抗剂将 用于分离对单个亚型的响应。 2.确定特定亚型的同时共激活是否具有 对响应的抑制、添加、增强或冗余效应 其他子类型。 3.确定长期接触激动剂是否下调了每种受体的表达 独立的亚型，以及对NE和EPI的反应是否增加或 减少了。 4.开始确定每种肾上腺素能受体亚型是否激活 一种不同的信号转导机制 对不同亚型反应的各种操作。 在下一个项目期间，我们希望澄清职能角色和 不同肾上腺素能受体亚型的相互作用。

It is now clear that there is a large family of different receptors for norepinephrine (NE) and epinephrine (EPI). At least 7 pharmacologically distinct adrenergic receptor subtypes (beta l-, beta 2-, beta3-, alpha 1a-, alpha1b-, alpha2a-, alpha2b-) have already been identified. However,little information is available on the importance of these subtypes in responses to transmitters. Since they often coexist on cells and have primary actions on the same second messenger systems, the net response to transmitter will often be determined by combined actions on multiple subtypes. Our major hypothesis is that NE and EPI cause their effects through simultaneous activation of many different receptor subtypes, and that these subtypes interact in complex ways to determine the net response of the cell. We propose to use primary cultures from one day old rat brain to characterize second messenger responses to individual subtypes, clarify their interactions, and determine how the cellular response to transmitter is controlled. The following specific aims will be addressed: 1. To determine the receptor subtypes involved in second messenger responses to NE and EPI. Alkylating agents and competitive antagonists will be used to isolate responses to individual subtypes. 2. To determine if simultaneous co-activation of particular subtypes have inhibitory, additive, potentiative or redundant effects on responses to other subtypes. 3. To determine whether chronic agonist exposure down-regulates each subtype independently, and whether responses to NE and EPI are increased or decreased. 4. To begin to determine whether each adrenergic receptor subtype activates a different signal transduction mechanism by examining the effect of various manipulations on responses to different subtypes. During the next project period we hope to clarify the functional roles and interactions of the different adrenergic receptor subtypes.